Abstract

Social isolation is a well-established technique for inducing early adversity but, in rodent models, the need of parental care makes it difficult to distinguish the effects of social deprivation from the consequences of nutritional deficiencies. Zebrafish do not require parental care, allowing separation of social deprivation from nutritional deprivation, and have emerged as a promising model to study ontogeny of normal and pathological behaviors relevant for human neuropsychological disorders. Previous reports of life-long isolation in zebrafish showed some consistency with mammalian literature, depicting later social deficits and locomotor hyperactivity. However, unlike reports of higher anxiety and stress behavior in isolated rodents and primates, behavioral responses were tapered in isolated fish. To examine whether life-long developmental isolation has a dampening effect on zebrafish endocrine stress response, we applied stressors to zebrafish siblings that were either isolated or socialized, and compared their whole-body cortisol levels with non-stressed control siblings kept in low-housing densities. Utilizing previously validated paradigms (exposure to novel tank and unpredictable chronic stress), we exposed separate groups (n = 9–14, mixed-sex) of social and isolated zebrafish to acute and chronic stressors and measured their cortisol levels. A univariate ANOVA and post-hoc Tukey’s HSD tests confirmed that compared to socially raised control fish, developmental isolation did not increase baseline cortisol levels in zebrafish. Additionally, compared to the non-stressed condition, application of both acute and chronic stressors significantly increased cortisol levels in isolated fish and, to a similar degree, to socially raised fish. Our findings suggest that zebrafish isolation studies may help separate effects of social deprivation from nonsocial aspects of early adversity. These studies further substantiate the use of developmental isolation in zebrafish, particularly with acute and chronic stress paradigms, for modeling neuropsychological disorders.

• LAY SUMMARY

• A difficult childhood can make humans react more frequently or severely to later stress and modeling this effect in animals can help explain how and why early stress affects subsequent mental and physical health. Early social isolation does not affect later response to stressful situations in adult zebrafish, providing us with a model of psychiatric disorders that allows separation of effects of poor physical environments (lacking food, shelter, etc.) from poor social environments (lack of appropriate socialization).

摘要

社会隔离是诱发早期逆境的行之有效的技术，但是，在啮齿动物模型中，需要父母照料使人难以将社会剥夺的影响与营养缺乏的后果区分开来。斑马鱼不需要父母的照料，可以将社会剥夺与营养剥夺区分开，并且已经成为研究人类神经心理学疾病的正常和病理行为的个体存在的有前途的模型。以前关于斑马鱼终生隔离的报道显示与哺乳动物文献有一定的一致性，描述了后来的社会缺陷和运动过度活跃。但是，与孤立的啮齿动物和灵长类动物的焦虑和压力行为较高的报道不同，孤立的鱼的行为反应呈锥形。为了检验终身发育隔离对斑马鱼内分泌应激反应是否具有抑制作用，我们将应激源应用于被隔离或社会化的斑马鱼兄弟姐妹，并将其全身皮质醇水平与保持在低矮住房中的非压力对照兄弟姐妹进行比较密度。利用先前验证的范例（暴露于新型水箱和不可预测的慢性压力），我们将社交和隔离斑马鱼的单独组（n = 9-14，混合性别）暴露于急性和慢性压力源，并测量其皮质醇水平。单变量方差分析和事后Tukey的HSD测试证实，与社交饲养的对照鱼相比，发育隔离不会增加斑马鱼的基线皮质醇水平。此外，与非压力状态相比，急性和慢性应激源的施用显着提高了离体鱼类的皮质醇水平，并且与社交饲养鱼类的皮质醇水平相似。我们的发现表明，斑马鱼隔离研究可能有助于将社会剥夺的影响与早期逆境的非社会方面分开。这些研究进一步证实了斑马鱼中发育隔离的应用，尤其是在急性和慢性应激范例中，对神经心理疾病的建模。

• 图层摘要

• 艰难的童年可能会使人类对以后的压力反应更加频繁或更严重，对动物的这种效应进行建模可以帮助解释早期压力如何以及为什么会影响随后的身心健康。早期的社会隔离不会影响成年斑马鱼对压力状况的后期反应，这为我们提供了一种精神疾病模型，可以将不良的身体环境（缺乏食物，住所等）的影响与不良的社会环境（缺乏适当的社交活动）区分开来）。